Inhibition of activated cdc42-associated kinase 1
View Patent ↗Compounds, compositions, and methods for specific inhibition of activated cdc42-associated kinase 1 (Ack1) are provided.
1. A method for inhibiting the biologic activity of activated cdc42-associated kinase I (Ack1), comprising contacting Ack1 with an amount of a compound of Formula I effective to inhibit the biologic activity of Ack1:
or a pharmaceutically acceptable salt thereof, wherein each of R 1 and R 2 is selected from the group consisting of: R 4 —O—, H, and
and
R 3 is
wherein R 4 is a C 1 -C 6 alkyl or H;
R 5 is a C 3 -C 8 cylcloalkyl, benzyl,
and
R 6 is F, Cl, or OMe; and
R 7 is a C 1 -C 3 alkyl.
2. The method of claim 1 , wherein the method is carried out in vitro.
3. The method of claim 1 , wherein the compound is capable of inhibiting the biologic activity of Ack1 at an IC 50 of about 5 nM or less.
4. A method for inhibiting the biologic activity of activated cdc42-associated kinase I (Ack1) in a cell, comprising contacting a cell expressing Ack1 with an amount of a compound of Formula I effective to inhibit the biologic activity of Ack 1 in the cell:
or a pharmaceutically acceptable salt thereof,
wherein each of R 1 and R 2 is selected from the group consisting of: R 4 —O—, H, and
and
R 3 is
wherein R 4 is a C 1 -C 6 alkyl or H;
R 5 is a C 3 -C 8 cycloalkyl, benzyl,
and
R 6 is F, Cl, or OMe; and
R 7 is a C 1 -C 3 alkyl.
5. The method of claim 4 , wherein the method is carried out in vitro.
6. The method of claim 4 , wherein the compound is capable of inhibiting the biologic activity of Ack1 at an IC 50 of about 5 nM or less.
7. The method of claim 4 , wherein the cell is a cancer cell.
8. The method of claim 4 , wherein the cell is a neuron.
9. The method of claim 1 , wherein the compound of Formula I is in a composition comprising a carrier.
10. The method of claim 9 , wherein the method is carried out in vitro.
11. The method of claim 9 , wherein the compound is capable of inhibiting the biologic activity of Ack1 at an IC 50 of about 5 nM or less.
12. The method of claim 9 , wherein the carrier is a pharmaceutically acceptable carrier.
13. The method of claim 4 , wherein the compound of Formula I is in a composition comprising a carrier.
14. The method of claim 13 , wherein the method is carried out in vitro.
15. The method of claim 13 , wherein the compound is capable of inhibiting the biologic activity of Ack1 at an IC 50 of about 5 nM or less.
16. The method of claim 13 , wherein the cell is a cancer cell.
17. The method of claim 13 , wherein the cell is a neuron.
18. The method of claim 13 , wherein the carrier is a pharmaceutically acceptable carrier.
19. The method of claim 1 wherein R 1 is H 3 CO—; R 2 is
and R 3 is
20. The method of claim 1 wherein R 1 is H 3 CO—; R 2 is
and R 3 is
21. The method of claim 1 wherein R 1 is H 3 CO—; R 2 is
and R 3 is
22. The method of claim 1 wherein R 1 is H 3 CO—; R 2 is
and R 3 is
23. The method of claim 1 wherein R 1 is
R 2 is H 3 CO—; and R 3 is
24. The method of claim 1 wherein R 1 is H; R 2 is H; and R 3 is